We will produce and determine the feasibility and/or efficacy of a (1) tissue culture grown inactivated influenza vaccine administered with or without an adjuvant (Novasomes), (2) tissue culture grown "live" cold reassortant influenza vaccine administered with or without an adjuvant, and (3) recombinant subunit influenza vaccine administered with or without adjuvant. Initial studies to determine feasibility of these types of vaccines will be determined by measuring the antibody response elicited in a rat model and comparing it to that obtained with egg grown influenza virus. The vaccine method(s) that produces a vaccine that elicits an antibody response equal to or greater than that of the egg grown virus will be used to produce pilot lot(s) of the avian/human reassortant virus(es) (provided by sponsor, sponsor collaborator or produced in house). The pilot lots will be produced and safety tested according to cGMP guidelines & tested in additional animal model(s), cotton rats and1or ferrets, for protection against virus challenge. The vaccine that protects animals from virus challenge at a level comparable to (or better than ) the current influenza vaccine will be used for phase l studied following submission/approval of an IND.